DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-19, of record, 6/8/2023 are pending. Prosecution on the merits commences for claims 1-19.
PRIORITY
The instant application, filed 6/8/23, is a CONTINUATION of US PAT 11,713,337, filed 12/30/2021, is a CONTINUATION of PCT/US20/40720, filed 07-02-2020, which claims priority to US Provisional Application No. 62/869,831, filed 07/02/2019. Thus, the earliest possible priority for the instant application is 07/02/2019.
CLAIMS
Independent claim 1 is drawn to a fusion peptide comprising a laminin alpha1 fragment and a VEGF heparan sulphate binding fragment:
Claim 1. A peptide comprising
(1) an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 4,
(2) a flexible linker, and
(3) SEQ ID NO: 5.
SEQ ID NO:4 comprises the laminin fragment of A-S-I-K-V-A-V-S-A
SEQ ID NO:5 comprises the VEGF heparan sulphate binding fragment of D-K-P-R-R
SEQ ID NO: 3 comprises ASIKVAVSA-GG-DKPRR
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application Publication No. 2010/0322862 to Ruoslahti, of record, in view of US Patent Application Publication No. 2007/0238684 to Hallek, of record, US Patent No. 6,921,663 to Mizuguchi of record, and US Patent No. 5,211,657 to Yamada of record. Claim 1 is directed to, at least, “A peptide comprising: (a) a first portion consisting of SEQ ID NO: 4 linked via a flexible linker to a second portion consisting of SEQ ID NO: 5.” This rejection is modified in response to Applicant’s amendments to the claims.
With regard to claims 1-3, Ruoslahti discloses cell-penetrating peptides comprising NP-1 base sequences of KXXR (CendR peptides) which, when complexed to a cargo, aids in increasing the uptake of the cargo into cells via NRP-1 directed endocytosis (Abstract, paragraphs [0008], [0010], [0013]-[0016], [0026], [0099]-[0100], [0102]-[0105], [0116], [0151], [0158]-[0159], [0176], [0197], [0208], [0221], [0226]-[0227], [0229]-[0230], [0246], [0259]-[0260], [0281], [0283]-[0284], [0289]-[0292], [0296]-[0298]; [0334]-[0341], [0382], FIG 1). Ruoslahti discloses the VEGF peptide fragment DKPRR functions as a CendR peptide (paragraph [0298]), which is identical to instantly claimed SEQ ID NO: 5.
Ruoslahti discloses DKPRR can be fused to the N-terminal of a targeting or homing peptide, including RGD sequences, wherein use of the targeting/homing peptide directs cargo to a target tissue or cell, and the CendR peptides increase uptake (paragraphs [0030]-[0031], [0033]-[0034], [0037]-[0038], [0166]-[0168], [0181]-[0184], [0218], [0290]-[0292], [0310], [0315]-[0325], and [0328]-[0330]).
Ruoslahti discloses the cargo for cellular uptake includes a virus, a viral particle, or a viral capsid (paragraphs [0158]-[0159], [0197], and [0259]-[0260]). Ruoslahti discloses a virus can encode a gene for the CendR peptides, and express the CendR peptide as part of the viral coat, wherein the virus, expressing the CendR peptide, delivers a heterologous protein molecule to target cells in vitro or in vivo (paragraphs [0277], [0293]-[0298], [0314], [0411]-[0428], [0437]-[0448], Example 2, Example 3). Ruoslahti discloses the homing/targeting peptide can be any peptide that targets a specific tissue or cell by binding a receptor at a target tissue or cell (paragraphs [0315]-[0325], [0328]-[0330]).
Thus, with regard to instant claims 1-3, Ruoslahti discloses an amino acid peptide comprising a portion consisting of SEQ ID NO:5 linked to a peptide linker to a portion consisting of a homing/targeting peptide:
PNG
media_image1.png
180
562
media_image1.png
Greyscale
However, Ruoslahti does not disclose wherein the targeting peptide is a peptide comprising a laminin fragment of A-S-I-K-V-S-A, according to SEQ ID NO:5.
Hallek discloses recombinant AAV viruses can comprise heterologous targeting peptides inserted into their viral capsid, wherein the heterologous homing peptides are directed to specific surface receptors, which aid in directing the recombinant AAV viruses to specific tissues and/or cells (Abstract, paragraphs [0001]-[0002], [0006], [0009]-[0010], [0016]-[0017], [0021]). Hallek discloses one specific cell-surface receptor that can be targeted by the recombinant AAV is the laminin receptor, by use of a targeting peptide derived from a laminin-α1 chain peptide fragment P1 (QAGTFALRGDNPQG) having an RGD sequence (paragraph [0021]). Hallek discloses the introduction of targeting ligands into the AAV capsid is based on the successful introduction of targeting ligands into the capsids of other viruses, including adenovirus (paragraph [0006]). Thus Hallek establishes AAV viral vectors comprise laminin receptor targeting peptides derived from laminin-α1 chain peptide fragment.
Mizuguchi discloses recombinant adenovirus vectors comprising heterologous targeting peptides inserted into their viral capsid (Abstract, column 2, lines 30-33, column 3, lines 60-64, column 4, lines 35-49). Mizuguchi discloses targeting peptides include RGD containing peptides, as well as a TSASIKVAV peptide that targets the laminin receptor (column 4, lines 35-41).
Yamada discloses functional fragments of laminin (abstract). Yamada discloses functional fragment PA22-2, and its derivatives PA22-3 and PA22-4, are derived from laminin-α1 chain and are active for, and can be used for, cell adhesion, cell growth, heparin binding, and neurite outgrowth (column 2, lines 15-18; column 3, lines 26-30, Example 6; Table III). Yamada also discloses functional fragment PA26, which comprises an RGD sequence, are derived from laminin-α1 chain and is active for, and can be used for, cell adhesion, cell growth (Example 7, column 3, lines 26-30, Table III). The amino acid sequences for PA22-2, PA22-3, PA-22-4 and PA-26 are:
PA22-2 XSRARQAASIKVAVSADR
PA22-3 XKRQAASIKVAVS
PA22-4 XIKVAVSADR
PA26 XFALRGDNPQG
Yamada’s PA26 fragment comprises Hallek’s laminin-derived targeting peptide:
PA26 XFALRGDNPQG
Hallek QAGTFALRGDNPQG
Yamada’s P22-2 fragment comprises Mizuguchi’s laminin-derived targeting peptide, and comprises instant SEQ ID NO: 4:
PA22-2 XSRARQAASIKVAVSADR
Mizugichi TSAASIKVAV
SEQ ID NO:4 ASIKVAVSA
It would have been obvious to combine the disclosure of Ruoslahti, on an amino acid peptide comprising SEQ ID NO:5 linked to a homing/targeting peptide via a peptide linker, complexed with a viral vector cargo, further with the disclosures of Hallek, Mizuguchi and Yamada to arrive at the claimed invention. Ruoslahti discloses any targeting peptide can be used in the invention (paragraph [0170]-[0173]). Hallek establishes AAV vectors comprise capsids having heterologous targeting peptides derived from laminin can be used to target recombinant AAV vectors to specific cell and/or tissue types. Mizuguchi establishes recombinant adenoviral vectors comprise capsids having heterologous targeting peptides derived from laminin can be used to target recombinant adenoviral vectors to specific cell and/or tissue types. Yamada establishes the laminin-derived targeting peptides of Hallek and Mizuguchi are known fragments of laminin suitable for cell adhesion. It would have been obvious to use Yamada’s P22-2 in Ruoslahti’s CendR peptide comprising SEQ ID NO:5, because Hallek’s, Mizuguchi’s, and Yamada’s laminin-derived peptide fragments are explicitly taught as being useful for targeting/cell adhesion. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
With regard to claim 4, Ruoslahti discloses the CendR peptides can be formulated as a pharmaceutical composition further comprising a therapeutic agent (paragraphs [0350]-[0355]).
With regard to claim 5, Ruoslahti discloses the therapeutic agent includes a virus, peptide, small molecule, antibodies or nucleic acids (paragraph [0158]-[0159], [0197], and [0259]-[0260], [0336]-[0337]).
With regard to claim 6, Ruoslahti discloses the therapeutic agent includes nucleic acids which when administered to a patient express a peptide, which reads on gene therapy, absent evidence to the contrary (Paragraphs [0115], [0158]-[0159], [0197], [0259]-[0260], [0388]-[0389], [0341]).
With regard to claim 8, Ruoslahti discloses the CendR proteins are encoded on genetic constructs (paragraph [0277]) as well as in a phage, and expressed from its capsid (Example 2, Example 3). Thus, Ruoslahti discloses the CendR proteins are encoded on a polynucleotide.
With regard to claim 9, Ruoslahti discloses the CendR proteins are encoded in a phage and expressed from its capsid (paragraphs [0277], [0293]-[0298], [0314], [0411]-[0428], [0437]-[0448], Example 2, Example 3). Thus, Ruoslahti discloses the polynucleotide encoding the CendR protein is inserted within a sequence encoding a viral capsid protein.
With regard to claim 9, since the CendR proteins of Ruoslahti are encoded and expressed from a phage capsid (Example 2, Example 3, paragraphs [0293], [0298]), the polynucleotide encoding the CendR gene must be operably linked to a promoter, absent evidence to the contrary.
To the extent Applicant argues that the CendR peptides encoded and expressed from the phage reduced to practice do not meet the structural requirements of claim 9, Ruoslahti discloses phage encode and express a recombinant CendR peptide from its capsid (Example 2, Example 3, paragraph [0293], [0298]). Ruoslahti discloses the viruses comprise CendR peptides in their capsids, and utilize them for cell entry (Example 2, Example 3, paragraphs [0298], [0281]). Ruoslahti discloses the CendR peptide can be encoded in any virus, virus particle, virus capsid or phage capsid (paragraphs [0158]-[0160], [0281], [0308]). However, Ruoslahti does not show that the recombinant CendR peptide encoded on a polynucleotide inserted into a sequence encoding the viral capsid comprises a promoter.
Hallek discloses recombinant AAV viruses can comprise heterologous targeting peptides inserted into their viral capsid, wherein the heterologous homing peptides are directed to specific surface receptors, which aid in directing the recombinant AAV viruses to specific tissues and/or cells (Abstract, paragraphs [0001]-[0002], [0006], [0009]-[0010], [0016]-[0017], [0021]). Hallek discloses the targeting peptides are encoding on polynucleotides that are inserted into the AAV genes encoding the capsid protein (paragraphs [0016], [0026], [0028], [0069]). Hallek discloses AAV genes are driven by AAV ITRs (paragraph [0002]), which thus function as a promoter.
Thus, it would have been obvious to encode the CendR proteins on a nucleic acid and operably link the CendR protein to a promoter. MPEP 2143 (I)(A), Combining prior art elements according to known methods to yield predictable results. In the instant case, the prior art included each element claimed, although not in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference, and in combination each element merely performs the same function as it does separately.
With regard to claims 10, 12 and 18-19, Ruoslahti discloses the CendR-[linker]-targeting peptides are cell penetrating peptides, and are used in methods of delivery to a cell or tissue comprising contacting the cell with the CendR-[linker]-homing peptide (paragraphs [0008], [0049]-[0051], [0108], [0166], [0289]-[0292]).
With regard to claims 11, 13, and 17, which require wherein use of the CendR-[linker]-targeting peptides results in increased delivery of the agent, or allows for transduction of the agent into the cell or tissue, compared to delivery into the cell in the absence of the peptide, Ruoslahti discloses the CendR-[linker]- targeting peptides facilitate increased enhanced entry of their cargo into cells, as the targeting peptides concentrates the cargo at the target cell, while the cell penetrating peptides facilitate internalization (paragraphs [0026], [0108], [0112], [0152]-[0156], [0166], [0232], [0250]-[0251], [0289]-[0292], [0315]).
With regard to claim 13, Ruoslahti discloses the CendR-[linker]-targeting peptide is coupled with the cargo via covalent or non-covalent association (paragraphs [0020], [0039]-[0040], [0173]-[0176]).
With regard to claims 14-16, Ruoslahti discloses the CendR-[linker]-targeting peptides can be used to deliver therapeutic agents to retinal tissue (paragraphs [0036], [0042], [0044], [0187], [0194], [0202], [0320], [0321]) and can be used for the treatment of macular degeneration, which reads on an ocular degenerative disease (paragraph [0341]).
Conclusion
No claims are allowed. No claims are free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY A ARON whose telephone number is (571)272-2789. The examiner can normally be reached Monday-Friday 9AM-5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
KAA
/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633